The development of efficient strategies for the stereoselective construction of privileged heterocyclic systems is an important objective in chemical synthesis and pharmaceutical sciences. Over the last decade, N-heterocyclic carbene (NHC) catalysis has provided opportunities for the development of new transformations based on polarity reversal or Umpolung reactivity. The exploration of these unconventional reactivity patterns with new electrophilic coupling partners facilitates advances in synthesis and provides access to bioactive natural products and unique, drug-like scaffolds. Substituted imidazoles are a privileged structural motif that is prevalent in pharmaceutical small molecules with diverse biological activities, including inflammation, HIV, depression, and various other disease areas.
There are several methods for the synthesis of substituted imidazoles and one approach involves the conversion of readily accessible imidazolidinones to the related imidazoles through functional group transformation. However, unlike the related oxazolones, new asymmetric methods involving imidazolidinones are scarce in the literature. There have been several recent reports involving the use of alkylidene oxazolones in enantioselective processes, likely due to the ability to access unnatural amino acids from these readily available precursors, but the related alkylidene imidazolidinones have received less attention. It was thought that Michael acceptors with such a heterocyclic framework combined with α,β-unsaturated aldehydes under carbene catalysis conditions could provide access to novel chiral imidazoles through a formal [4+2] annulation, but the use of such electron rich conjugate acceptors has not been investigated in the preparation of bicyclic dihydropyranoimidazolones.